1. Field of the Invention
This invention pertains generally to treatment of uterine fibroids, and more particularly to ultrasound therapy of uterine fibroids.
2. Description of Related Art
Uterine fibroids, also known as leiomyomas or myomas, are the most common solid pelvic tumor occurring in women, and are the reason for nearly 30% of hysterectomies performed in the U.S. Further, it has been estimated that 25-50% of women of reproductive age have one or more uterine fibroids, and the incidence is as much as 9 times higher in black women than in white women. Depending on the size, number and location of the fibroids, symptoms can be severe, and often include excessive or persistent menorrhagia, pelvic pain and cramping, pressure, urinary problems, constipation, anemia, or infertility. Another concern is the degeneration of fibroids to malignant leiomyosarcomas, at an incidence rate of approximately 0.5%.
FIGS. 1A and 1B are anatomical sketches contrasting a healthy patient 10 having a normal uterus 22 with a second patient 12 having a uterus showing growth of uterine fibroids in various regions. Fibroids are nodules of well-differentiated smooth muscle encased in fibrous tissue that grow in or on the wall of the uterus, with some reports of myomas demonstrating skeletal muscle differentiation. Fibroids range in size from approximately 0.5 cm to greater than 10 cm in diameter, and may grow as submucosal fibroids 30 just beneath the endometrium 14 (submucous), as intramural fibroids 36 within the myometrium 16 (intramural), or subserosal fibroids 28 beneath the serosa. They may also be pedunculated, and reside either within the uterine cavity 22 (pedunculated submucosal fibroids 34), or outside the uterus 22 in the pelvic cavity (pedunculated subserosal fibroids 32).
Treatment options for women considering bearing children are limited. The most common and permanent treatment for uterine fibroids is surgical removal of the uterus (hysterectomy), particularly in women approaching menopause. Although a permanent solution for fibroids, hysterectomy is a major surgical procedure associated with significant risk of mortality/morbidity including fever, wound infection, excessive blood loss, increased risk for transfusion, and trauma to the bladder and surrounding tissues. Recent improvements in hysterectomies performed using a vaginal approach have demonstrated reductions in blood loss, post-op complications, length of hospital stay, and overall cost. However, vaginal hysterectomies are not recommended for patients presenting with a large fibroid uterus.
For pre-menopausal women wishing to retain their uterus for reproductive, psychological or hormonal reasons, myomectomy (surgical removal of fibroids) can be a less invasive alternative to hysterectomy. The procedure may be performed via open laparotomy, or via a number of advanced laparoscopic and hysteroscopic surgical techniques. For women considering childbearing, preferred surgery is the open myomectomy in order to preserve the structural integrity of the uterine wall—the ability to apply multiple layers of suturing is severely limited for laparoscopic procedures. While complications are similar to those of hysterectomy, the complication rate is reduced from 25% to as low as 14.8%, and fertility may be improved, with pregnancy rates reported as high as 74%. However, the incidence of post-operative adhesions may be as high as 89%, and the risk of recurring fibroids requiring additional surgery or hysterectomy is 15-25%.
Hormonal therapies such as gonadotrophin releasing hormone (GnRH) agonists can be used to induce artificial menopause resulting in a 30-40% decrease in fibroid size, and a 40-50% reduction in uterine volume. The side effects experienced with hormonal therapies are similar to symptoms often associated with menopause (hot flashes, irregular vaginal bleeding, vaginal dryness, headaches, and depression). However, prolonged use may result in excessive bone loss, and the fibroids will return to their pre-treatment volumes within 3 months if treatment is discontinued. Rather than a long term treatment option, hormonal therapies are often used prior to myomectomy to reduce the size of the uterus and the fibroids thus facilitating the surgical procedure.
Uterine artery embolization (UAE) is a minimally-invasive surgical procedure used to treat fibroids by obstructing their blood supply. A catheter, advanced into the uterine artery under fluoroscopic guidance, is used to inject polyvinyl alcohol particles resulting in immediate obstruction of blood flow. Clinical studies indicate that UAE reduces fibroid volume by approximately 35-60%, and has been effective in 85% of the patients. Complications of the procedure include risk of allergic reaction to medications, infection, contrast-induced renal failure, uterine perforation, sexual dysfunction, and post-procedure pain attributed to the ischemic necrosis. Fibroid sloughing requiring additional surgery occurs in about 10% of the patients.
Laparoscopic myoma coagulation (myolysis) is a minimally-invasive procedure in which a laser or a radiofrequency (RF) needle is used to thermally coagulate and necrose uterine fibroids and their vascular supply. Both modalities can be used to thermally coagulate and reduce the size of uterine fibroids by as much as 40 to 50%. However, a recent clinical study using an RF needle electrode with extendible secondary electrodes to treat large fibroids demonstrated the ability to produce a 5 cm diameter region of necrosis resulting in as much a 77% reduction in fibroid volume. Yet spatial control of the pattern is very difficult, if not impossible. An advantage of myolysis performed using a laser fiber is that treatment can be guided and monitored in real time with MR thermal monitoring techniques. However, since the propagation of energy, and hence coagulation of tissue, is limited to a radial distance of less than 1 cm from the applicator at a single puncture, high power levels, multiple punctures (sometimes >50) and longer treatment times are often required to treat commonly occurring large myomas (5+ cm diameter) using either RF or laser modality. Techniques using either sequential insertions or multiple, simultaneously implanted laser fibers around the circumference of the fibroid have been used to coagulate the outer boundary, thus destroying the blood supply and shrinking the fibroid. Although major complications with this technique are rare, the risk of post-operative adhesions increases with the greater number of device insertions required to heat larger fibroids. Control of thermal coagulation with these technologies is determined by applied power only, with no dynamic angular or longitudinal spatial control of heating along the length of the applicator, or radially/angularly from it.
The feasibility of using cryotherapy for treatment of fibroids has been investigated. Initial studies demonstrated an overall reduction in fibroid size of only 10%; recent studies have shown clinical results similar to those obtained by other minimally-invasive treatments with mean volume reductions up to 65%. Furthermore, this technology can be used with interventional MR imaging for visualization and guidance of the cryoneedles, and monitoring of the freezing procedure. Control of the freezing zone is problematic. Complications of this technique are similar to those associated with thermal coagulation methods. The applicator diameters range 3-5 mm, and are introduced with trocars and introducer sheaths similar to our proposed procedure.
In some, the above thermal techniques (e.g. cryotherapy or high-temperature thermal ablation) have at least one of the following limitations: inability to spatially control the distribution of energy output to conform to the fibroid volume, inadequate single treatment volumes requiring multiple device insertions (increases risk of adhesions), long procedural times, or limited use due to proximity of critical tissue structures (e.g., bladder, bowel). These limitations may reduce their effectiveness and overall applicability to consistently and safely treat symptomatic fibroids.
High-intensity externally-focused ultrasound (HIFU) is a another, non-invasive method used to generate well-localized thermal damage deep within the body, while possibly avoiding damage to the overlaying or surrounding tissues. Although this technique is non-invasive and capable of precise coagulation of tissue, long treatment times (>2 hours) are required to treat small tissue volumes (12 cm3), access to fibroids located in proximity to bowel or bladder is limited, and lack of adequate acoustic window and pre-focal heating limits this technology to accessible small fibroids. Significant reported complications include thermal damage or burns in deep tissue, bowel, and superficial tissue layers, including the skin beneath the acoustic interface.
There is a substantial clinical need for a minimally-invasive alternative to traditional open surgical approaches with the promise of less morbidity and recovery time, faster procedure time, and lower cost. Interstitial ultrasound has potential to provide a superior minimally-invasive heating technique for the laparoscopic treatment of uterine fibroids with the promise of more precise and thorough targeting, accessibility to a larger number of fibroids, faster procedure times, and repeatable performance acceptable to the gynecological surgeon.